Cytokine

History

Some consider that the first cytokine was identified in 1957. It is about the Interféron, definite at the time by its antiviral activity (an infected cell transmits a message for its neighbor so that this one is protected from the viral infection). But one can as estimate as it is about endogenous pyrogenic, identified in 1948, like a factor emitted during the infection to induce the fever.

The term “ cytokine ” was introduced in 1974 by Stanley Cohen.

In a few decades, the cytokines knew an explosion of interest in the fields of research and the medicine which led to an avalanche of information. It was proposed the implication of the cytokines in the processes related to the Embryogenèse, the Reproduction (biology), the Gestation, the Hématopoïèse, the immunizing response, the Inflammation. But the cytokines also contribute to pathological situations like: chronic autoimmunity, sepsis, cancer, inflammatory diseases (entérocolites, disease of Crohn, polyarthritis rhumatoïde, psoriasis, etc), viral hepatites, the infection by the HIV… The cytokines can be also therapeutic agents (e.g. G-CSF to facilitate the hematologic reconstitution…) or of the targets (e.g. TNF in disease of Crohn, polyarthritis rhumatoïde…)

The big family of the cytokines

Interleukine S

It is about cytokines gathered under this terminology without biochemical relationship nor of function, but classified by convenience with the liking of the discoveries. The term was created in 1979 to one time when only two were known interleukines (IL-1 and IL-2). At the beginning of 2006 one is with 31 cytokines under the heading IT

Chimiokines or Chémokines

Defines the whole of the low-weight cytokines having jointly a capacity chimiotactic. The nomenclature is based on precise points of their structure (CCL1 with CCL28, CXCL1 with CXCL16, XCL1 & 2, CX3CL1)

the family of the " tumor necrosis factor" (TNF)

Members resulting from a common ancestral gene, also being able to be on the surface of the cells

" Colony stimulating factors" (CSF)

Cytokines playing a part in the Hématopoïèse, but also being able to activate the mature Leucocyte S.

" Transforming growth factors " (TGF)

Growth factors implied in the cicatrization and the negative control of the Ignition.

Receiver

The receivers membrane S seem to be able to be classified under a certain number of families according to the fields which constitute them:

Récepteurs of the hématopoïétines
Récepteurs of IFNs
related Récepteurs with the superfamille of the immunoglobulins
Récepteurs of the chémokines (with 7 transmembrane fields)
Récepteurs of the family of the TNF
the receivers can be released from the surface of the cells and modify the function of the cytokines as soluble receivers

Not to confuse Cytokine and hormone

The cytokines are distinguished from the Hormone S by four basic principles

sources:

The cytokines are secreted by several cellular types. The hormones as for them are secreted by only one type of specialized and located cell.

targets:

The cells mainly targeted by the cytokines are numerous and include the hematopoietic cells, whereas in the case of the hormones, those are more specific of their target cells.

activities:

The cytokines have a broad spectrum of activity. There exists even a strong redundancy. As for the hormones, they have primarily a single or more restricted activity.

modes of action:

The hormones have an endocrine mode of action (act remotely after being conveyed by blood), whereas for the cytokines it is multiple: paracrine, autocrine juxtacrine and endocrine.

Examples of cytokines

lymphokines or monokines (obsolete terms).
chémokines.
interleukines.
Certains growth factors which, while binding to receivers of membrane surface, will stimulate the cellular division shares many common properties with the cytokines.

Cytokines and influenza

The virus Highly pathogenic H5N1 of the Avian flu, as the H1N1 responsible for the Spanish Grippe of 1918-1919 starts at the man (not vaccinated neither immunized) as in the animal (not vaccinated nor immunized) an abnormally sharp reaction of the immune system. The secretion of cytokines is so brutal and important that instead of controlling the ignition it causes organic failures sometimes mortals. That also arrives at the time of some " influenzas malignes" where a very abundant production of cytokines causes for example an acute edema of the lung, which then loses its elasticity and thus of its functionality. The expression “ storm of cytokines ” describes this phenomenon.

At the beginning of 2003, the team of Robert Webster showed that the H5N1 thwarted one of the functions of the immune system which is the “answer cytokine”
S.H. Seo and Al showed into 2004 that the resistance of the virus has (H5N1) HP with the antiviral activity of the cytokines was related on the presence of gene NS1 and more precisely to the glutamic acid in position 92 of the sequence of amino-acids. Pigs infected in experiments with a recombining virus reconstituted by opposite genetics, carrying gene of nonstructural protein (NS1) of the virus (H5N1) isolated in HongKong developed an influenza clinically more severe than during an infection by the virus " sauvage".
De more, in vitro studies on culture of infected porcine pulmonary cells, show that the addition in the middle of culture, of interféron alpha, gamma and of factor necroses tumoral alpha, does not deteriorate the replication of the virus has (H5N1).
En 2007, the autopsy of a human fetus reached by the H5N1; that of a Chinese woman (24 years), died of the H5N1 HP 9 days after the primary symptoms revealed the presence of virus H5N1 in the placenta and the liver of the fetus, but especially in its lungs where it however caused less damage than in those of the mother. The study suggests that these weak damage can be explained by the immaturity of the immune system of the fetus, which did not produce a storm of cytokines and chemokines vis-a-vis the virus.

It seems to exist nevertheless birds (ex: ducks) carrying asymptomatic in which the virus does not start this “ storm of cytokines ”. It would be interesting to include/understand how they are protected some.
Chez the man this phenomenon seems more particularly to touch the young people and adults in the full force of the age, which would explain why the children and the elderly were touched by the Spanish influenza and are it also less by the H5N1 since its appearance in 1997 and its extension in 2003.
On knows only two viruses, characterized both by a genetic characteristic, able to produce of such damage and so quickly, the H1N1 of 1918, and the variable H5N1 HP recently appeared. The elderly often develop pneumonic forms with superinfections. The expectant mother can die or fall through about it. A retrospective study showed that the fetuses and embryos which survived the pandemia of 1918 in mothers having contracted the virus seem to have kept durable after-effects of them but the responsibility for the cytokines was not studied for the Embryon or the Fœtus.

(Source: Menno de Jong, Natural Medicine, Oct. 2006)

Primary sources

"CYTOKINES" , under the direction of J. - M. Cavaillon with the Editions Masson , 1996
" MOLECULAR MEDIATORS: CYTOKINES" , J. - M. Cavaillon, in " Encyclopedia off Molecular Concealment Biology and Molecular Medicine " , 2nd Edition, vol. 8Wiley-VCH Verlag, Weinheim, Germany, 2005, p 431-460

Simple: Cytokine

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